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US4943587A Expired / Lapsed US ⏱️ 0.0 years remaining

Hydroxamate derivatives of selected nonsteroidal antiinflammatory acyl residues and their use for cyclooxygenase and 5-lipoxygenase inhibition

Assignee: Warner Lambert Co LLC
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Filing: 1988-05-19
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Granted: 1990-07-24
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Expires: 2008-05-19
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Abstract

Abstract The present invention is novel selected hydroxamic acid derivatives of acyl residues of selected NSAIDS, i.e. having 5-lipoxygenase and cyclooxygenase inhibiting properties, pharmaceutical compositions for treating conditions advantageously affected by the inhibition and methods for treating these conditions in mammals, including humans suffering therefor.

Inventors

  • 👤 Wiaczeslaw A. Cetenko
  • 👤 David T. Connor
  • 👤 Daniel L. Flynn
  • 👤 Jagadish C. Sircar

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-10 01:26
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/04; C07C; C07C257/00; C07C257/04; C07C257/06; A; A61; A61P; A61P11/00; A61P11/08; A61P25/00; A61P25/04; A61P29/00; A61P3/00; A61P37/00; A61P37/08; C07C317/00; C07C317/26; C07C317/32; C07C317/34; C07C317/38; C07C317/40; C07D209/10; C07D209/18; C07D209/26; C07D461/00; C07C2602/00; C07C2602/02; C07C2602/04; C07C2602/08

Claims Analysis

Total Claims: 12
Claim 1
Independent Claim 304 words
A compound of the formula (Ia) ##STR55## and pharmaceutically acceptable cid addition or base salt thereof in which (i) R 1 is hydrogen, lower alkyl or acyl; (ii) R 2 is H, lower alkyl, cycloalkyl of from three to twelve carbon atoms of which from three to seven carbons are ring carbons, aryl arylalkyl or heteroaryl with the overall proviso that R 1 and R 2 cannot both be hydrogen; and (iii) R 3 is hydrogen, phenylmethyl, allyl, vinyl, isopropenyl or ##STR56## in which R 1 .sbsb.a is selected from the group consisting of benzene, naphthalene, biphenyl and substituted benzene, naphthalene and biphenyl radicals in which said substituent is selected from the group consisting of halogen, lower alkyl, lower alkylthio, lower alkoxy, trifluoromethyl, phenoxy, lower alkyl phenoxy, lower alkoxy phenoxy, halogenophenoxy, trifluoroacetyl, difluoroacetyl, monofluoroacetyl, di-lower alkyl sulfamyl, lower alkanyl, di-lower alkyl carboxamido, cyano, carb-lower alkoxy, trifluoromethylthio, lower alkyl sulfinyl, lower alkylsulfonyl, benzylthio, lower alkylbenzylthio, lower alkoxybenzylthio, halogenobenzylthio, mercapto, nitro, amino, di-(lower alkyl)amino, lower alkylamino, lower alkanoylamino, hydroxy, lower alkanoyloxy, trifluoroacetoxy, difluoroacetoxy, monofluoroacetoxy, benzyloxy, lower alkylbenzyloxy, lower alkoxybenzyloxy, and halogenobenzyloxy; R 2 .sbsb.a is selected from the group consisting of hydrogen, lower alkenyl and lower alkyl; R 3 .sbsb.a is selected from the group consisting of hydrogen and lower alkyl; R 4 .sbsb.a is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, fluorine and trifluoromethyl; R 5 .sbsb.a is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower alkoxy, nitro, amino, lower alkylamino, di(lower alkyl) amino, lower alkanoylamino, lower alkanoyl, lower alkylamino, bis(hydroxy lower alkyl)amino, 1-pyrrolidino, 4-methyl-1-piperazinyl, 4-morpholinyl, cyano, amino lower alkyl, mono-lower alkylamino lower alkyl, di-lower alkyl amino lower alkyl, trifluoromethyl, halogen, di(lower alkyl)sulfamyl, benzylthio, lower alkylbenzylthio, lower alkoxybenzylthio, halogenobenzylthio, benzyloxy, lower alkylbenzyloxy, lower alkoxybenzyloxy, halogenobenzyloxy, lower alkenyl, lower alkenyloxy, 1-azacyclopropyl, cyclopropyl (lower alkoxy) methoxy, and cyclobutyl(lower alkoxy) methoxy.
Claim 2
Dependent Claim 304 words
A compound of the formula (Ia) ##STR55## and pharmaceutically acceptable cid addition or base salt thereof in which (i) R 1 is hydrogen, lower alkyl or acyl; (ii) R 2 is H, lower alkyl, cycloalkyl of from three to twelve carbon atoms of which from three to seven carbons are ring carbons, aryl arylalkyl or heteroaryl with the overall proviso that R 1 and R 2 cannot both be hydrogen; and (iii) R 3 is hydrogen, phenylmethyl, allyl, vinyl, isopropenyl or ##STR56## in which R 1 .sbsb.a is selected from the group consisting of benzene, naphthalene, biphenyl and substituted benzene, naphthalene and biphenyl radicals in which said substituent is selected from the group consisting of halogen, lower alkyl, lower alkylthio, lower alkoxy, trifluoromethyl, phenoxy, lower alkyl phenoxy, lower alkoxy phenoxy, halogenophenoxy, trifluoroacetyl, difluoroacetyl, monofluoroacetyl, di-lower alkyl sulfamyl, lower alkanyl, di-lower alkyl carboxamido, cyano, carb-lower alkoxy, trifluoromethylthio, lower alkyl sulfinyl, lower alkylsulfonyl, benzylthio, lower alkylbenzylthio, lower alkoxybenzylthio, halogenobenzylthio, mercapto, nitro, amino, di-(lower alkyl)amino, lower alkylamino, lower alkanoylamino, hydroxy, lower alkanoyloxy, trifluoroacetoxy, difluoroacetoxy, monofluoroacetoxy, benzyloxy, lower alkylbenzyloxy, lower alkoxybenzyloxy, and halogenobenzyloxy; R 2 .sbsb.a is selected from the group consisting of hydrogen, lower alkenyl and lower alkyl; R 3 .sbsb.a is selected from the group consisting of hydrogen and lower alkyl; R 4 .sbsb.a is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy, fluorine and trifluoromethyl; R 5 .sbsb.a is selected from the group consisting of hydrogen, hydroxy, lower alkyl, lower alkoxy, nitro, amino, lower alkylamino, di(lower alkyl) amino, lower alkanoylamino, lower alkanoyl, lower alkylamino, bis(hydroxy lower alkyl)amino, 1-pyrrolidino, 4-methyl-1-piperazinyl, 4-morpholinyl, cyano, amino lower alkyl, mono-lower alkylamino lower alkyl, di-lower alkyl amino lower alkyl, trifluoromethyl, halogen, di(lower alkyl)sulfamyl, benzylthio, lower alkylbenzylthio, lower alkoxybenzylthio, halogenobenzylthio, benzyloxy, lower alkylbenzyloxy, lower alkoxybenzyloxy, halogenobenzyloxy, lower alkenyl, lower alkenyloxy, 1-azacyclopropyl, cyclopropyl (lower alkoxy) methoxy, and cyclobutyl(lower alkoxy) methoxy.
Claim 3
Dependent Claim 8 words
A compound of claim 1 which is 1-(4-chlorobenzoyl-N-hydroxy-5-methoxy-N,2-dimethyl-1H-indole-3-acetamide.
Claim 4
Dependent Claim 8 words
A compound of claim 1 which is 1-(4-chlorobenzoyl-N,5-dimethoxy-2-methyl-1H-indole-3-acetamide.
Claim 5
Dependent Claim 8 words
A compound of claim 1 which is 1-(4-chlorobenzoyl-N-hydroxy-5-methoxy-2-methyl-N-(1-methylethyl)-1H-indole-3-acetamide.
Claim 6
Dependent Claim 9 words
A compound of claim 1 which is 1-(4-chlorobenzoyl-N-cyclohexyl-N-hydroxy-5-methoxy-2-methyl-l1H -indole-3acetamide.
Claim 7
Dependent Claim 8 words
A compound of claim 1 which is 1-(4-chlorobenzoyl)-N,5-dimethoxy-N,2-dimethyl-1H-indole-3-acetamide.
Claim 8
Dependent Claim 8 words
A compound of claim 1 which is 1-(4-chlorobenzoyl-N-hydroxy-5-methoxy-2-methyl-N-phenyl-1H-indole-3-acetamide.
Claim 9
Dependent Claim 8 words
A compound of claim 1 which is 1-(4-chlorobenzoyl)-N-benzyl-N-hydroxy-5-methoxy-2-methyl-lH-indole-3-acetamide.
Claim 10
Dependent Claim 18 words
A compound of claim 1 which is ##STR57## wherein R 1 and R 2 are as defined above.
Claim 11
Dependent Claim 39 words
A pharmaceutical composition for the treatment of prophylaxis of a condition advantageously affected by inhibition of lipoxygenase and cyclooxygenase comprising an effective amount of a compound of the formula Ia of claim 1 together with a pharmaceutically acceptable carrier.
Claim 12
Dependent Claim 34 words
A method of treating a condition advantageously affected by inhibtion of 5-lipoxygenase and cyclooxygenase in a human suffering therefrom comprising administering a compound of the formula Ia of claim 1 in unit dosage form.

References Cited (Backward Citations)

US3624103A Cited
US4092430A Cited
US4173577A Cited
US4029815A Cited
EP0039051A2 Cited
EP0196184A2 Cited
EP0196674A2 Cited

USPTO Annuity & Maintenance Windows

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